- Email: [email protected]
P.2.g.001 Correlation between smoking and depression
P.2.g Affictive disorders and antidepressants - Other (clinical) carbamazepine, and l579±382.4 for valproate. The most commonly prescribed other medications were antipsychotic medications (51.1%), benzodiazepines (17%) and antidepressants (9%). The initial assessment consisted in a clinical evaluation, and a plasmatic dosage of different mood stabilisers. This dosage was realized using the electrodes method for lithium and the immunopolarization fluorescence technique (TDX Abbott) for carbamazepine and valproate. The follow-up was ensured by the same medical team with at least four consultations per year including the same monitoring elements. The adherence with mood stabilisers was defined by the absence of plasma levels below the therapeutic ranges during the follow-up. The therapeutic ranges were 0.61.0mmoVL for lithium, 4-l0mgIL for carbamazepine and 50100mgIL for sodium valproate. Results: Mean plasma levels of mood stabilizers were 0.68±0.22mmoVL (range, 0.25-1.18mmoVL) for lithium, 7.9±2.2mgIL (range, 0.15-l4mgIL) for carbamazepine, and 72.8±23.0mgIL (range, l7.4-135.2mgIL) for valproate. Forty nine (55.7%) of patients have met criteria for nonadherence. The rates of non-adherence were 78.9% in patients receiving lithium, 19.4% in patients receiving carbamazepine, and 62.4% in patients receiving valproate. Backward stepwise logistic regression demonstrated that non-adherence was correlated with number of recurrences during the follow-up, number of previous mood stabiliser substitutions, delay of mood stabiliser prescription and association with antipsychotic medications. Conclusions: In the follow up study, rates of mood stabiliser non-adherence are high in bipolar I patients. This finding may be related to mood stabiliser modifications and the subtherapeutic mood stabiliser levels. To improve long term treatment outcome, we should reinforce monitoring of patients and associate psychoeducational measures.
P.2.f Affective disorders and antidepressants - Bipolar disorders (basic)
S47l
surveys suggested that some genes are contributed to the onset of this disorder. A common remedy of bipolar disorder is lithium. This drug is comparatively effective, but it has higher incidence of adverse effects, because lithium has a narrow therapeutic window. Therefore, new drugs which have both efficacy and few side effects are needed. The purpose of our present work was to investigate the involvement of DGK/3 in bipolar disorder. For this purpose, we performed some behavioral tests using DGK/3 knockout (KO) mice. Methods: We conducted 24 hours locomotor activity test and open field test to examine the activity in DGK/3 KO mice and its wild-type (WT) littermates. We also analyzed the severity of anxious and depression in DGK/3 KO mice by the behavioral methods, such as elevated plus maze test, forced swim test and tail suspension test. Furthermore, we subjected DGK/3 KO mice and its WT littermate to Y-maze test and Morris water maze test, in order to examine their cognitive function. Finally, the effect of chronic mood stabilizer, lithium treatment on the behavior was tested in DGK/3 KO mice and its WT littermates. Statistics: Statistical analysis was performed by SPSS statistics software. The data was compared using Student's t-tests or analysis of variance followed by Dunnett test. Results: In locomotor activity test (p < 0.05) and open field test (p<0.01), DGK/3 KO mice were more active than their WT littermates. In comparison with WT mice, DGK/3 KO mice stayed for long time in anxiogenic place of open field test (p < 0.05) and elevated plus maze test (p < 0.05). DGK/3 KO mice also showed lower depression like behaviors in forced swim test (p < 0.05) and tail suspension test (p < 0.001). In addition, DGK/3 KO mice exhibited cognitive impairment in Y-maze test (p < 0.01) and Morris water maze test (p < 0.05). In these abnormal behaviors DGK/3 KO mice showed, lower anxiety was improved by the chronic treatment of lithium chloride (p < 0.05). Conclusion: These profiles of DGK/3 KO mice were similar to the mania phase of bipolar I disorder patient. These findings suggested that alteration of DGK/3 function may be related to the manic symptom. Further studies will be needed to clarify the relationship between DGK/3 and bipolar disorder.
Ip.2.f.0011 Mania-like behavioural abnormalities of diacylglycerol kinase
II knockout mice
K. Kakefuda1 " A. O~agi1, K. Tsuruma1, M. Shimazawa1, K. Yokota2 , Y. Shirai , K. Horie4 , N. Sait03 , 1. Takeda4 , 1 GijU Pharmaceutical University, Biofimctional H. Hara1 . Evaluation Molecular Pharmacology, GijU, Japan; 2 Carna Biosciences Incorporated, Pharmacology, Kobe, Japan; 3 KtJbe University, Biosignal Research Center, Kobe, Japan; 4 Graduate School ofMedicine Osaka University, Department of Social and Environmental Medicine, Suita, Japan
Background and Purpose: Diacylglycerol kinase (DGK) is an enzyme which phosphorylates diacylglycerol to produce phosphatidic acid. Of 10 mammalian DGK isozymes, DGK/3 is widely distributed in the central nervous system, such regions as the olfactory bulb, cerebral cortex, striatum and hippocampus, and in mice the expression of this enzyme increases dramatically after the second week, which is coincident with the synapse formation in the brain. In addition, it has been reported that the COOHterminal of DGK/3 protein is lacking in bipolar disorder patients. Bipolar disorder is a mental illness causing unusual shifts in mood from the heights of mania to the depths of depression. The lifetime prevalence of this disease is about 1%, and epidemiological
P.2.g Affective disorders and antidepressants - Other (clinical) 1P.2.g.0011 Correlation between smoking and depression 1. Gabos Grecu1 " M. Gabos Grecu1, T. Moica1, A. Vesa 1, R. Crisan2 , M. Florea3 , G. Buicu1, C. Gabos Grecu1. 1First Clinic ofPsychiatry, Psychiatry, Targu-Mures, Romania; 2 Clinical County Hospital, Gynecology, Targu-Mures, Romania; 3 Private Health Services, General Medicine, Targu-Mures, Romania
Background: In persons with mental illness the percentage of smokers is between 50-90% compared with 24% in the general population [1,3]. Depressive patients have a probability of 40% less to give up smoking compare to a smoker who doesn't suffer of depression. Depression or depressive symptoms may be part of the clinical picture of withdrawal from nicotine (DSM IV TR), and clinical studies conducted in twins shows that severe depression occurs with greater frequency in smokers compared to non-smokers [2]. Purpose of paper: Studying the correlations between tobacco consumption and depression, to identify the effects of smoking
S472
P.2.g Affictive disorders and antidepressants - Other (clinical)
on patients with symptoms of Major Depressive Disorder (MDD) and to identify demographic factors that affect in any way the consumption of tobacco and the evolution of the disease. Material and Method: we evaluated a number of 242 patients diagnosed with MDD, hospitalized in Clinic of Psychiatry I, in Tirgu-Mures, between the 1 of April 2007 and the 31 of December 2008. Patients were divided into two groups: 121 patients with MDD and consumption of tobacco, and 121 patients with MDD and the lack of smoking. Work tools: Hamilton depression scale with 21 items, DSM IV TR criteria for diagnosing depression, statistical program (Graph Pad). Results: Of the 159 patients 58 women smoke (36%) and 101 (64%) are non-smokers. Also of the 83 male patients 63 (76%) smoke and 20 (24%) do not smoke. The most affected age decade for patients with MDD is between 50-59 years for both sexes in both groups of smokers and non-smoking group. Consumption of tobacco is more common in urban areas 54% (130) than rural areas 46% (112). In the group of smokers with depression percentage of patients with weight loss was higher (63%) than in the non-smokers group 40%. In patients with MDD the presence of suicide ideas and attempted suicide is more frequent among smokers - 36%, compared to 12% in nonsmoking patients. Conclusions: Number of patients with MDD female is larger than male. We found a higher percentage of patients smoking men who suffer from depression compared with those who do not smoke, which can confirm the effect of tobacco on the development of depressive symptoms. The most affected age decade is between 50-59 years in both sexes in both groups of smokers and nonsmokers. The number of smokers with MDD is higher in urban zones than in rural zones due to industrialization. In smokers with MDD were found aggravating circumstances the most common being interfamilial conflicts and medical causes. Among smokers depressive patients most frequently identified type of personality was anxious type. Weight reduction is more important in depressive patients among smokers compared to non-smokers. Psychomotor restlessness was seen in all smoker patients. This is why they increased the amount of cigarettes smoked and worsening insomnia. Associated with depression, smoking increases the risk of suicide by increasing the frequency of suicidal ideas and suicide attempts. As a general conclusion we can say that smoking has a negative impact on patients' quality of life and the evolution of depression in the long term even under pharmacological treatment. It is therefore an urgent need for multidisciplinary collaboration between family doctors, psychiatrists, pneumologists and psychotherapists to help these patients to stop smoking permanently. References
[1] Cosmo H, Nicola Mcclure - Anxiethy and depression, our questions answerd, Churchi11livingstone, pg. 19-59, 1998 [2] Kendler KS., Neale MC, MacLean CJ, Heath AC, Eaves LJ, Kessler RC.-Smoking and major depression: A causal analysis, Arch Gen Psychiatry, nr. 50 pg.36-43, 1993 [3] Park E. 2008 The influencing factors on suicide attempt among adolescents in South Korea. Taehan Kanho Hakhoe Chi; 38: 465-73.
1P.2.g.0021 Mean platelet volume in patients with major depression: effect of escitalopram treatment F. Canan1 " A. Ataoglu1 . 1Duzce University Medical School, Psychiatry, Duzce, Turkey Purpose: Strong evidence supported by numerous epidemiological studies indicates that depression is an independent predictor of cardiovascular mortality and morbidity [1,2]. The relationship between major depression and increased platelet activity has been previously indicated by several studies. First objective of the present study was to examine mean platelet volume (MPV), which is a practical indicator of platelet activity, in depressed subjects in comparison with healthy volunteers. Our second objective was to investigate whether escitalopram treatment would change platelet activity which was evaluated by MPV in patients with major depression. Methods: Fifteen patients (11 women and 4 men), meeting the DSM-IV criteria for a current episode of major depressive disorder (MDD) (mean±SD age, 37±1O years) were recruited, as well as 17 physically and mentally healthy comparison subjects (11 women and 6 men) (mean±SD age, 35±6 years), who were similar in age and sex to the patients who were depressed. The eligible patients were physically healthy, aged 18 years or older. All of them had a baseline Montgomery-Asberg Depression Rating Scale (MADRS) total score of at least 22. MPV and platelet count (pLC) of the controls and patients were measured at the entry to the study. Severity of depressive symptoms and response to escitalopram treatment was assessed by using MADRS. After 8 weeks of open-label treatment with the selective serotonin reuptake inhibitor escitalopram (10-20 mg/d), the patients with depression were readmitted and the measurements were repeated. Results: In comparison with the control group, the depressed group exhibited greater platelet activity as detected by increased MPV (p < 0.001). MPV was found to be significantly decreased compared to the baseline value after 8 weeks treatment with escitalopram (p < 0.05). There was also a significant decline in PLC (p < 0.05). An average of 15.1 (± 4.6) points decline was noted in MADRS scores which reached statistical significance (p < 0.001). The correlation between the change in MADRS and MPV was poor and not statistically significant (r=0.29, p: 0.28). MPV; after treatment, was still higher in depressed patients (10.56±0.92) than in normal controls (10.01±0.66). However, statistically significant difference between the groups disappeared (p > 0.05) at the end of the study. Conclusion: The present study has shown that escitalopram improved MPV in patients with MDD by decreasing it to a favorable degree when compared with healthy subjects. Escitalopram was also found to decrease PLC. There was not a correlation between the changes in MPV and MADRS scores. According to these findings, escitalopram seems to have an antiplatelet effect independent of its antidepressant properties. Therefore, the use of escitalopram may be advised for patients with major depression and a comorbidity of coronary artery disease. On the other hand, it should be kept in mind that antiplatelet effect of this drug may, like other SSRIs [3], be associated with increased bleeding risk. Further studies establishing the antiplatelet effect of escitalopram in MDD patients with other comorbidities are warranted. References
[1] Musselman, D.L., Evans, D.L., Nemeroff, C.B., 1998 The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry 55:580-592.
P.2.f Affective disorders and antidepressants - Bipolar disorders (basic)
S47l
surveys suggested that some genes are contributed to the onset of this disorder. A common remedy of bipolar disorder is lithium. This drug is comparatively effective, but it has higher incidence of adverse effects, because lithium has a narrow therapeutic window. Therefore, new drugs which have both efficacy and few side effects are needed. The purpose of our present work was to investigate the involvement of DGK/3 in bipolar disorder. For this purpose, we performed some behavioral tests using DGK/3 knockout (KO) mice. Methods: We conducted 24 hours locomotor activity test and open field test to examine the activity in DGK/3 KO mice and its wild-type (WT) littermates. We also analyzed the severity of anxious and depression in DGK/3 KO mice by the behavioral methods, such as elevated plus maze test, forced swim test and tail suspension test. Furthermore, we subjected DGK/3 KO mice and its WT littermate to Y-maze test and Morris water maze test, in order to examine their cognitive function. Finally, the effect of chronic mood stabilizer, lithium treatment on the behavior was tested in DGK/3 KO mice and its WT littermates. Statistics: Statistical analysis was performed by SPSS statistics software. The data was compared using Student's t-tests or analysis of variance followed by Dunnett test. Results: In locomotor activity test (p < 0.05) and open field test (p<0.01), DGK/3 KO mice were more active than their WT littermates. In comparison with WT mice, DGK/3 KO mice stayed for long time in anxiogenic place of open field test (p < 0.05) and elevated plus maze test (p < 0.05). DGK/3 KO mice also showed lower depression like behaviors in forced swim test (p < 0.05) and tail suspension test (p < 0.001). In addition, DGK/3 KO mice exhibited cognitive impairment in Y-maze test (p < 0.01) and Morris water maze test (p < 0.05). In these abnormal behaviors DGK/3 KO mice showed, lower anxiety was improved by the chronic treatment of lithium chloride (p < 0.05). Conclusion: These profiles of DGK/3 KO mice were similar to the mania phase of bipolar I disorder patient. These findings suggested that alteration of DGK/3 function may be related to the manic symptom. Further studies will be needed to clarify the relationship between DGK/3 and bipolar disorder.
Ip.2.f.0011 Mania-like behavioural abnormalities of diacylglycerol kinase
II knockout mice
K. Kakefuda1 " A. O~agi1, K. Tsuruma1, M. Shimazawa1, K. Yokota2 , Y. Shirai , K. Horie4 , N. Sait03 , 1. Takeda4 , 1 GijU Pharmaceutical University, Biofimctional H. Hara1 . Evaluation Molecular Pharmacology, GijU, Japan; 2 Carna Biosciences Incorporated, Pharmacology, Kobe, Japan; 3 KtJbe University, Biosignal Research Center, Kobe, Japan; 4 Graduate School ofMedicine Osaka University, Department of Social and Environmental Medicine, Suita, Japan
Background and Purpose: Diacylglycerol kinase (DGK) is an enzyme which phosphorylates diacylglycerol to produce phosphatidic acid. Of 10 mammalian DGK isozymes, DGK/3 is widely distributed in the central nervous system, such regions as the olfactory bulb, cerebral cortex, striatum and hippocampus, and in mice the expression of this enzyme increases dramatically after the second week, which is coincident with the synapse formation in the brain. In addition, it has been reported that the COOHterminal of DGK/3 protein is lacking in bipolar disorder patients. Bipolar disorder is a mental illness causing unusual shifts in mood from the heights of mania to the depths of depression. The lifetime prevalence of this disease is about 1%, and epidemiological
P.2.g Affective disorders and antidepressants - Other (clinical) 1P.2.g.0011 Correlation between smoking and depression 1. Gabos Grecu1 " M. Gabos Grecu1, T. Moica1, A. Vesa 1, R. Crisan2 , M. Florea3 , G. Buicu1, C. Gabos Grecu1. 1First Clinic ofPsychiatry, Psychiatry, Targu-Mures, Romania; 2 Clinical County Hospital, Gynecology, Targu-Mures, Romania; 3 Private Health Services, General Medicine, Targu-Mures, Romania
Background: In persons with mental illness the percentage of smokers is between 50-90% compared with 24% in the general population [1,3]. Depressive patients have a probability of 40% less to give up smoking compare to a smoker who doesn't suffer of depression. Depression or depressive symptoms may be part of the clinical picture of withdrawal from nicotine (DSM IV TR), and clinical studies conducted in twins shows that severe depression occurs with greater frequency in smokers compared to non-smokers [2]. Purpose of paper: Studying the correlations between tobacco consumption and depression, to identify the effects of smoking
S472
P.2.g Affictive disorders and antidepressants - Other (clinical)
on patients with symptoms of Major Depressive Disorder (MDD) and to identify demographic factors that affect in any way the consumption of tobacco and the evolution of the disease. Material and Method: we evaluated a number of 242 patients diagnosed with MDD, hospitalized in Clinic of Psychiatry I, in Tirgu-Mures, between the 1 of April 2007 and the 31 of December 2008. Patients were divided into two groups: 121 patients with MDD and consumption of tobacco, and 121 patients with MDD and the lack of smoking. Work tools: Hamilton depression scale with 21 items, DSM IV TR criteria for diagnosing depression, statistical program (Graph Pad). Results: Of the 159 patients 58 women smoke (36%) and 101 (64%) are non-smokers. Also of the 83 male patients 63 (76%) smoke and 20 (24%) do not smoke. The most affected age decade for patients with MDD is between 50-59 years for both sexes in both groups of smokers and non-smoking group. Consumption of tobacco is more common in urban areas 54% (130) than rural areas 46% (112). In the group of smokers with depression percentage of patients with weight loss was higher (63%) than in the non-smokers group 40%. In patients with MDD the presence of suicide ideas and attempted suicide is more frequent among smokers - 36%, compared to 12% in nonsmoking patients. Conclusions: Number of patients with MDD female is larger than male. We found a higher percentage of patients smoking men who suffer from depression compared with those who do not smoke, which can confirm the effect of tobacco on the development of depressive symptoms. The most affected age decade is between 50-59 years in both sexes in both groups of smokers and nonsmokers. The number of smokers with MDD is higher in urban zones than in rural zones due to industrialization. In smokers with MDD were found aggravating circumstances the most common being interfamilial conflicts and medical causes. Among smokers depressive patients most frequently identified type of personality was anxious type. Weight reduction is more important in depressive patients among smokers compared to non-smokers. Psychomotor restlessness was seen in all smoker patients. This is why they increased the amount of cigarettes smoked and worsening insomnia. Associated with depression, smoking increases the risk of suicide by increasing the frequency of suicidal ideas and suicide attempts. As a general conclusion we can say that smoking has a negative impact on patients' quality of life and the evolution of depression in the long term even under pharmacological treatment. It is therefore an urgent need for multidisciplinary collaboration between family doctors, psychiatrists, pneumologists and psychotherapists to help these patients to stop smoking permanently. References
[1] Cosmo H, Nicola Mcclure - Anxiethy and depression, our questions answerd, Churchi11livingstone, pg. 19-59, 1998 [2] Kendler KS., Neale MC, MacLean CJ, Heath AC, Eaves LJ, Kessler RC.-Smoking and major depression: A causal analysis, Arch Gen Psychiatry, nr. 50 pg.36-43, 1993 [3] Park E. 2008 The influencing factors on suicide attempt among adolescents in South Korea. Taehan Kanho Hakhoe Chi; 38: 465-73.
1P.2.g.0021 Mean platelet volume in patients with major depression: effect of escitalopram treatment F. Canan1 " A. Ataoglu1 . 1Duzce University Medical School, Psychiatry, Duzce, Turkey Purpose: Strong evidence supported by numerous epidemiological studies indicates that depression is an independent predictor of cardiovascular mortality and morbidity [1,2]. The relationship between major depression and increased platelet activity has been previously indicated by several studies. First objective of the present study was to examine mean platelet volume (MPV), which is a practical indicator of platelet activity, in depressed subjects in comparison with healthy volunteers. Our second objective was to investigate whether escitalopram treatment would change platelet activity which was evaluated by MPV in patients with major depression. Methods: Fifteen patients (11 women and 4 men), meeting the DSM-IV criteria for a current episode of major depressive disorder (MDD) (mean±SD age, 37±1O years) were recruited, as well as 17 physically and mentally healthy comparison subjects (11 women and 6 men) (mean±SD age, 35±6 years), who were similar in age and sex to the patients who were depressed. The eligible patients were physically healthy, aged 18 years or older. All of them had a baseline Montgomery-Asberg Depression Rating Scale (MADRS) total score of at least 22. MPV and platelet count (pLC) of the controls and patients were measured at the entry to the study. Severity of depressive symptoms and response to escitalopram treatment was assessed by using MADRS. After 8 weeks of open-label treatment with the selective serotonin reuptake inhibitor escitalopram (10-20 mg/d), the patients with depression were readmitted and the measurements were repeated. Results: In comparison with the control group, the depressed group exhibited greater platelet activity as detected by increased MPV (p < 0.001). MPV was found to be significantly decreased compared to the baseline value after 8 weeks treatment with escitalopram (p < 0.05). There was also a significant decline in PLC (p < 0.05). An average of 15.1 (± 4.6) points decline was noted in MADRS scores which reached statistical significance (p < 0.001). The correlation between the change in MADRS and MPV was poor and not statistically significant (r=0.29, p: 0.28). MPV; after treatment, was still higher in depressed patients (10.56±0.92) than in normal controls (10.01±0.66). However, statistically significant difference between the groups disappeared (p > 0.05) at the end of the study. Conclusion: The present study has shown that escitalopram improved MPV in patients with MDD by decreasing it to a favorable degree when compared with healthy subjects. Escitalopram was also found to decrease PLC. There was not a correlation between the changes in MPV and MADRS scores. According to these findings, escitalopram seems to have an antiplatelet effect independent of its antidepressant properties. Therefore, the use of escitalopram may be advised for patients with major depression and a comorbidity of coronary artery disease. On the other hand, it should be kept in mind that antiplatelet effect of this drug may, like other SSRIs [3], be associated with increased bleeding risk. Further studies establishing the antiplatelet effect of escitalopram in MDD patients with other comorbidities are warranted. References
[1] Musselman, D.L., Evans, D.L., Nemeroff, C.B., 1998 The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry 55:580-592.